The product of duration and amount of proteinuria (proteinuria index) is a possible marker for glomerular and tubulointerstitial damage in IgA nephropathy

BACKGROUND/AIMS: IgA nephropathy (IgAN) is one of the major causes for chronic renal failure (CRF). Presence of massive proteinuria, hypertension, increased serum creatinine level and sclerotic histopathological changes of the glomerulus are known to be determinants for the progression of CRF. However, the relationships between duration of proteinuria/hematuria and histopathological changes, which may be correlated with the renal prognosis, have not been clarified. METHODS: A cross-sectional, univariate analysis of clinical parameters on the four glomerular and three tubulointerstitial histopathological grades in 57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. RESULTS: The age at the time of renal biopsy (35.2 +/- 13.0 years; mean +/- SD), average duration of proteinuria (5.3 +/- 5.8 years), mean urinary protein excretion (0.99 +/- 1.22 g/day), serum creatinine (Cr 0.97 +/- 0.28 mg/dl), Cr clearance (Ccr 75.5 +/- 29.4 ml/min), and blood urea nitrogen (BUN 15.4 +/- 3.9 mg/dl) were well correlated with both histopathological grades. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy was more significantly correlated with glomerular and tubulointerstitial histopathological grades and serum Cr. CONCLUSION: The natural course of IgAN is steadily progressive depending on the duration and amount of proteinuria. The product of these two factors (proteinuria index) may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN.     

Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes

A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.     

伴有慢性肾衰竭的马兜铃酸肾病与IgA肾病的配对研究

目的:了解伴有慢性肾衰竭的马兜铃酸肾病患者与IgA肾病患者的临床病理差异.方法:分析11例马兜铃酸肾病患者的临床病理资料,并与经肾活检确诊的IgA肾病患者进行配对比较.结果:两组患者的年龄、性别、血肌酐水平无明显差异(P>0.05),马兜铃酸肾病患者镜下血尿发生率低于IgA肾病患者(P<0.05).在血肌酐水平无明显差异时,马兜铃酸肾病患者血红蛋白浓度明显低于IgA肾病患者(P<0.01),尿蛋白定量和肾脏的长径少于IgA肾病患者(P<0.05).间质纤维化程度重于IgA肾病患者(P<0.05),而间质炎细胞浸润少(P<0.05).结论:伴有慢性肾衰竭的马兜铃酸肾病患者临床发展隐匿,与IgA肾病比较,肾小管间质损伤是造成肾功能损害的主要原因,因此要重视对马兜铃酸肾病的早期防治.     

A case of idiopathic chronic interstitial nephritis progressed to renal failure without proteinuria nor hematuria]

A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (beta 2-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis.     

Long-term prognosis of membranoproliferative glomerulonephritis type I. Significance of clinical and morphological parameters: an investigation of 220 cases

We carried out a retrospective investigation in 220 patients to assess the influence of various parameters on the long-term course of membranoproliferative glomerulonephritis (MPGN) type I. 50 patients (23%) died during the follow-up period of 59 months on average, in another 57 (26%) end-stage renal failure developed. 54 patients (24%) suffered from chronic renal failure, stable renal function (creatinine below 1.3 mg/dl) was preserved in 59 patients (27%). 5 years after biopsy 49% of the patients had already died or needed regular dialysis treatment; after 10 years this proportion increased to 64%. Morphological findings: The outcome was--with the exception of focal crescent formations--not determined by the severity of glomerular changes; the survival rate, however, decreased significantly, if tubulointerstitial lesions were present as defined by acute renal failure, interstitial fibrosis or a combination of both. Clinical parameters: A progressive deterioration of renal function and an increasing number of renal deaths was noticed, when elevated serum creatinine levels at the time of biopsy and high blood pressure values during the follow-up period were observed. 26 patients died from hypertension, 18 of whom before reaching end-stage renal failure. Nephrotic syndrome and the degree of proteinuria as well as antiphlogistic and immunosuppressive treatment did not influence the prognosis of MPGN type I.     

A case of childhood IgA nephropathy who developed rapidly progressive glomerulonephritis in one-year clinical course

A 10-year-old girl who presented with microscopic hematuria, proteinuria and normal renal function has been followed up for the past two years. At the first examination, renal biopsy revealed focal/segmental lesions accompanying by occaisional necrosis and small crescents. Diagnosis of IgA nephropathy was given by light, electron and immunofluorescent microscopic findings. She started on the treatment with dipyridamol and was followed up for one year without any serious complications. Thereafter, she suddenly developed severe deterioration of renal function (serum creatinine 2.7 mg/dl) with nephrotic syndrome and hypertension. The second renal biopsy done at this time indicated the presence of typical crescentic glomerulonephritis with mesangial proliferation. No vasculitis was noted. She was intensively treated with steroids, anticoagulants and other medication and responded fairly well clinically. The third renal biopsy performed 5 months afterwards demonstrated marked histological improvement, but there was still present mesangial proliferation and varied degrees of sclerotic changes with fibrocellular crescents. Focal interstitial fibrosis and collapsed tubules were also seen. At present, 5 months after the last renal biopsy, she has improved much better and her serum creatinine decreased to 1.9 mg/dl, although proteinuria of 3 g/day still persists. It is suggested that only a small segmental necrosis with crescent formation in IgA nephropathy should be considered as an important indicator of disease activity in the evaluation of prognosis.     

IgA nephropathy: prognostic significance of proteinuria and histological alterations

A retrospective study of 166 patients with IgA nephropathy was undertaken to clarify possible correlations between clinical and histological features, and the severity and prognosis of the disease. At the time of biopsy, impaired renal function, with creatinine clearance (Ccr) below 90 ml/min was found in 61 cases. At the final examination, after a mean follow-up period of 34 months, 82 patients had impaired renal function, 12 of these patients went into terminal renal failure requiring hemodialysis treatment. The presence of proteinuria of more than 1.0 g/day was closely correlated with impairment of renal function both at the time of biopsy and at the final observation. An unfavorable outcome was also anticipated in the presence of hypertension. In contrast, microhematuria, macrohematuria or high serum IgA levels did not appear to be related to the outcome. Histologically, sclerotic lesions such as mesangial or global sclerosis, interstitial fibrosis and tubular atrophy, and some active changes such as mesangial hypercellularity and tuft adhesion were more frequent and severe in patients with impaired renal function. Impressive localization of IgA and C3 in the mesangium as well as in capillary loops was observed more often in these patients. These results clearly indicate that IgA nephropathy may follow a slowly progressive course in about half of the patients, and that marked proteinuria and severe histological changes appear to correlate closely with an unfavorable course.     

Renal pathology in idiopathic membranous nephropathy: a new perspective

Histology findings in idiopathic membranous nephropathy (MGN) have been associated with the risk of renal failure, but whether they are independent of the clinical variables at the time of biopsy, predict rate of progression, or should guide therapy is uncertain. Renal biopsies of 389 adult MGN patients were evaluated semiquantitatively for interstitial fibrosis, tubular atrophy, vascular sclerosis, focal and segmental glomerulosclerosis lesions (FSGS), complement deposition, and stage and synchrony of deposits by electron microscopy (EM). Associations were tested between these findings and the rate of renal function decline (slope), renal survival, remission in proteinuria, and response to immunosuppression. Patients with a greater degree of tubulo-interstitial disease, vascular sclerosis, and secondary FSGS were older, had a higher mean arterial pressure, and a lower creatinine clearance at presentation. Although these histologic features were associated with a reduced renal survival, they did not predict this outcome independently of the baseline clinical variables nor did they correlate with the rate of decline in function or with baseline proteinuria. Furthermore, the severity of tubulo-interstitial and vascular lesions did not preclude a remission in proteinuria in those who received immunosuppressive therapy. Neither stage nor synchronicity of EM deposits nor the amount of complement deposition predicted renal survival but the latter did correlate with progression rate. In MGN, certain histologic changes are associated with renal survival outcome. However, the indicators of chronic injury are associated with age, blood pressure, and creatinine clearance at presentation and not with rate of disease progression or initial proteinuria.     

Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes

The following results were obtained in a long-term retrospective study including 250 patients with focal sclerosing glomerulonephritis: 1. The renal survival rate (RSR) was 90% at 5 years and 67% at 10 years, the average period of observation being 4.7 years. 2. Univariate analysis revealed that the following morphologic and clinical parameters are associated with an increased risk of terminal renal failure or death due to renal causes: a) Tubulointerstitial changes in the form of interstitial fibrosis, with or without acute renal failure; b) Advanced glomerular lesions; c) Advanced vascular alterations; d) Nephrotic syndrome present at the time of the biopsy; e) Elevated serum creatinine concentration at the time of the biopsy; f) Arterial hypertension at the time of the biopsy; g) Greater age at diagnosis; h) Male sex. 3. Multivariate survivorship analysis showed that tubulointerstitial changes and the presence of nephrotic syndrome at the time of biopsy are the only variables with significant independent predictive value for the outcome. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy.     

成人微小病变肾病综合征发生急性肾损伤的相关影响因素分析

目的探讨成人微小病变肾病综合征发生急性肾损伤( AKI)的相关影响因素。 方法回顾性分析2002年1月1日至2015年12月31日在解放军总医院病理诊断为微小病变肾病,临床表现为首发肾病综合征的成年患者。记录其横断面临床及病理指标,并将其分为AKI组及非AKI组进行比较。用单因素及多元Logistic回归分析与AKI发生相关的影响因素。并对AKI相关的各影响因素进行交互作用检验。 结果共纳入403例患者,男女比例为1∶1.13,肾活检时平均年龄为(39.5 ± 15.1)岁,其中118(29.3%)例发生了AKI。AKI组与非AKI组相比,年龄、性别、尿蛋白定量、血清白蛋白、血肌酐、血尿素氮、估算的肾小球率过滤、肾小管萎缩、肾间质病变差异均有统计学意义(P<0.05)。单因素Logistic回归分析显示高龄、男性、尿蛋白定量多、肾小管萎缩、肾间质水肿、间质纤维化及炎细胞浸润、高血压是成人微小病变肾病发生AKI的危险因素。交互作用检验表明血清白蛋白对AKI的作用受到肾间质纤维化的显著影响(P＝0.0 050),且在调整年龄分组、性别、高血压、尿蛋白定量、肾小管萎缩、肾间质水肿、肾间质炎细胞浸润混杂因素后,其交互作用仍显著(P＝0.0 263)。从多元Logistic回归分析可见,在无肾间质纤维化的人群中,血清白蛋白水平的升高是AKI的独立保护因素(调整后的OR 0.8,95%CI 0.7～ 0.9,P<0.001)。在有肾间质纤维化人群中,血清白蛋白的升高对AKI肾脏的保护作用不显著(调整后的OR 1.0,95%CI 0.9～1.0,P＝0.0 278)。 结论高龄、男性、尿蛋白定量多、肾小管萎缩、肾间质水肿、间质纤维化及炎细胞浸润、高血压是成人微小病变肾病综合征发生AKI的危险因素。血清白蛋白升高对AKI的保护作用受到肾间质纤维化的影响。     

Clinical features and natural history in adults with IgA nephropathy

Two different clinical syndromes might be observed at presentation in most patients with IgA nephropathy (IgAN): (1) an acute reversible episode of macroscopic hematuria or (2) asymptomatic urinary abnormalities. Patients in these groups differ by genetic markers, the severity of their histologic lesions, and the rate of progression to renal insufficiency. Macroscopic hematuria is more common in children, and its frequency decreases with increasing age. In our experience, most patients presenting in adulthood with macroscopic hematuria did not have proteinuria or microscopic hematuria prior to the episode of macroscopic hematuria, suggesting the onset of disease was indeed in adulthood. IgAN is not a benign disease. About 20% of patients reach end-stage renal failure after 20 years of clinical disease. Features generally associated with a poor prognosis include older age at onset, no history of recurrent macroscopic hematuria, hypertension, and consistent proteinuria. In some studies, men progressed more rapidly than women. Using the regression of Cox in the present study, the magnitude of proteinuria was the only clinical parameter that independently predicted progressive renal impairment.     

ANCA-related crescentic glomerulonephritis in systemic sclerosis: revisiting the "normotensive scleroderma renal crisis"

The scleroderma renal crisis is characterized by acute onset of severe hypertension and by rapidly progressive hyperreninemic renal failure. There is, however, a very limited subset of patients with rapidly progressive renal failure who remain normotensive and develop ANCA-positive crescentic glomerulonephritis. We report a case of normotensive acute renal failure secondary to anti-MPO antibody-associated crescentic glomerulonephritis in a patient with diffuse systemic sclerosis. She was referred to our department with normal blood pressure and no extrarenal clinical manifestation ofvasculitis. She presented with rapidly progressive renal failure, microscopic hematuria and minimal proteinuria. P-ANCA were positive by immunofluorescence, with ELISA-confirmed specificity for myeloperoxidase. Renal biopsy revealed typical features of pauciimmune glomerulonephritis with crescent formation and fibrinoid necrosis. The patient was initially treated with i.v. cyclophosphamide only. Because of ongoing deteriorating renal function, additional treatment with intravenous pulses of methylprednisolone followed by oral prednisone was started and allowed renal function improvement. After 9 months, serum creatinine had almost returned to normal level with minimal proteinuria, no hematuria and negative ANCA testing. Control kidney biopsy only revealed scar lesions. The association of ANCA-positive crescentic glomerulonephritis and systemic sclerosis is a very rare event. Treatment with intravenous cyclophosphamide and corticosteroids allows rapid and long-term improvement of renal function. The onset of typical scleroderma renal crisis triggered by high-dose corticosteroids is unlikely but requires a close follow-up of patients with overlapping systemic sclerosis. Diagnosis and treatment are discussed and previously published cases are reviewed.     

Disturbance of lymph circulation develops renal fibrosis in rats with or without contralateral nephrectomy

Background: The knowledge on renal lymphatics is very limited and their importance is often neglected in kidney transplantation surgery practice. Early papers demonstrated that acute ligation of hilar lymphatic ducts has a significant effect on sodium excretion and urine volume. However, the long‐term effects of hilar lymphatic ducts ligation on renal function and histology were not mentioned. Here we show the time course of renal lesions caused by long‐term ligation of renal hilar lymphatic vessels in rats with or without contralateral nephrectomy. Methods: Animals were divided into three groups: rats with bilateral renal lymphatic ducts ligation (2KL); rats with one renal ligation and another nephrectomy (1KL); sham‐operated rats (Sham). Proteinuria, serum creatinine value and creatinine clearance were monitored. Renal histology was examed by light microscopy. Further biochemical analysis was provided using real‐time polymerase chain reaction, immunostaining and western blot techniques. Results: From week 1 after ligation, both 1KL and 2KL rats developed severe proteinuria, whereas elevated serum creatinine and reduced creatinine clearance were observed from week 2. Histomorphological changes appeared in ligated kidneys at week 2, characterized by tubular damage, tubulointerstitial fibrosis and expansion of the mesangium. Overexpression of transforming growth factor‐β1 (TGF‐β1), Smad2/3, COL I genes and proteins were detected in 1KL and 2KL rats. Compared with 2KL rats, the changes in renal function and histology were more pronounced in 1KL rats. Conclusion: Disturbance of lymph circulation induced chronic renal failure and renal fibrosis, which were aggravated by lymphatic vessels ligation combined with contralateral nephrectomy. The effect of lymphatic ducts ligation on renal lesions may be explained by enhanced activation of the TGF‐β1/Smad signalling.     

Clinicopathological study of IgA nephropathy in adults: The influence of onset age on clinical and renal histological findings and on the effect of steroid therapy

Background. The prognosis of IgA nephropathy (IgAN) varies according to the patient's age. It usually affects children or young adults. However, the onset age for IgAN may be at middle-age or older. The influence of onset age on the clinical and renal histological findings of adult IgAN was investigated. Methods. We selected 39 IgAN patients in whom renal biopsy was performed within 2 years from the onset. The patients were divided into two groups according to onset age; early-onset group (under 35 years; group E) and late-onset group (over 35 years; group L). The clinical and histological findings and the response to steroid therapy were compared in the two groups. Results. (1) Clinically, the levels of proteinuria and hematuria in groups E and L were not different, but the creatinine clearance was lower in group L than in group E. Hypertension was frequent in group L (66.7%), but not in group E. (2) Histologically, the rate of glomerular obsolescence and the grades of interstitial fibrosis and arterio- and arteriolosclerosis were more advanced in group L than in group E. However, there were no differences in the grade of mesangial cell proliferation or mesangial matrix increase, nor were the rates of glomerular crescent and tuft adhesion formation different between the two groups. (3) The reduction of proteinuria and hematuria after 1-year steroid therapy was similar in the two groups. Conclusion. Onset age does not affect the severity of glomerular lesions and the effect of steroid therapy in the early phase of adult IgAN. However, advanced interstitial fibrosis and arterio- and arteriolosclerosis, which may be related to hypertension or the aging process, lead to impaired renal function in late-onset IgAN patients. Received: March 18, 1998 / Accepted: October 29, 1998     

Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy.

BACKGROUND: The course of idiopathic membranous nephropathy (iMN) is variable in untreated patients. Accurate prediction of renal outcome would allow optimal treatment decisions. We demonstrated that urinary beta2-microglobulin (beta2M) predicted prognosis in iMN with high sensitivity and specificity. It has been suggested that focal segmental glomerulosclerosis (FSGS) is a discriminative parameter with independent prognostic value. METHODS: We selected patients with iMN biopsied between 1988 and 2002. Biopsies were analysed for the presence of FSGS, interstitial fibrosis and vascular lesions. Serum creatinine, creatinine clearance, proteinuria and blood pressure were recorded at baseline. Outcome variables included remission of proteinuria, renal death (RD) defined as serum creatinine >135 micromol/l or increase of serum creatinine of >50%, or end-stage renal disease (ESRD). In a subgroup of patients, urinary beta2-microglobulin (beta2M) was measured. RESULTS: We included 53 patients (33M, 20F). Mean age was 51 years, serum creatinine 99 micromol/l, and proteinuria 7.0 g/10 mmol creatinine. FSGS was present in 22 patients. These patients were characterized by a higher serum creatinine at time of biopsy (P = 0.035), more severe interstitial fibrosis (P = 0.001) and higher stage of membranous nephropathy (P = 0.001). During follow-up 24 patients developed RD, almost equally distributed between patients with and without FSGS. Renal survival was numerically, but not significantly, lower in patients with FSGS. In Cox proportional hazard analysis, only serum creatinine at the time of biopsy was an independent predictor of RD or ESRD (P < 0.001). In patients with known urinary beta2M, there was no significant correlation with FSGS score (P = 0.174). CONCLUSION: FSGS is not an accurate prognostic marker in iMN. Histological scoring of FSGS is inferior to measurement of urinary proteins in predicting renal outcome in iMN.     

Primary focal sclerosing glomerulonephritis: A clinicopathological analysis

SUMMARY: The clinical and laboratory features, renal biopsy findings, and outcome of 68 patients with primary focal sclerosing glomerulonephritis were studied. the cumulative probability of not progressing to end-stage renal failure (ESRF) was 0.92 at 5 years and 0.73 at 10 years after presentation, and was significantly worse in patients with hypertension or severe renal impairment (serum creatinine >0.24 mmol/L) at presentation. Proteinuria of up to 1gm/day was associated with an excellent prognosis, whereas proteinuria of 1–3 gm/day and >3 gm/day had similar and poorer survivals. an adverse outcome was associated with, at presentation, age less than 30 years, hypertension, a family history of glomerulonephritis, cigarette smoking, impaired renal function, and heavy proteinuria. Renal biopsy findings which correlated with progressive renal failure included a higher percentage of glomeruli with global or segmental sclerosis, and the degrees of tubular atrophy, interstitial fibrosis, interstitial inflammation and arterial thickening. During follow-up the degrees of renal impairment and proteinuria, persistence or development of hypertension, transient decreases of renal function of >10%, and the total number of red cells and casts on centrifuged urine microscopy were all predictive of progressive renal disease. Multivariate analysis demonstrated that the indices with adverse effects on outcome induced all of the above except tubulointerstitial and vascular changes on renal biopsy. It is concluded that the prognosis may be better than has been suggested in the literature. It is possible to predict which patients are likely to have an adverse outcome, and this should assist with therapeutic decisions likely to retard progression of disease.     

Primary focal sclerosing glomerulonephritis: A clinicopathological analysis

The clinical and laboratory features, renal biopsy findings, and outcome of 68 patients with primary focal sclerosing glomerulonephritis were studied. The cumulative probability of not progressing to end-stage renal failure (ESRF) was 0.92 at 5 years and 0.73 at 10 years after presentation, and was significantly worse in patients with hypertension or severe renal impairment (serum creatinine >0.24 mmol/L) at presentation. Proteinuria of up to 1gm/day was associated with an excellent prognosis, whereas proteinuria of 1–3 gm/day and >3 gm/day had similar and poorer survivals. An adverse outcome was associated with, at presentation, age less than 30 years, hypertension, a family history of glomerulonephritis, cigarette smoking, impaired renal function, and heavy proteinuria. Renal biopsy findings which correlated with progressive renal failure included a higher percentage of glomeruli with global or segmental sclerosis, and the degrees of tubular atrophy, interstitial fibrosis, interstitial inflammation and arterial thickening. During follow-up the degrees of renal impairment and proteinuria, persistence or development of hypertension, transient decreases of renal function of >10%, and the total number of red cells and casts on centrifuged urine microscopy were all predictive of progressive renal disease. Multivariate analysis demonstrated that the indices with adverse effects on outcome included all of the above except tubulointerstitial and vascular changes on renal biopsy. It is concluded that the prognosis may be better than has been suggested in the literature. It is possible to predict which patients are likely to have an adverse outcome, and this should assist with therapeutic decisions likely to retard progression of disease.     

少量蛋白尿和（或）血尿IgA肾病临床病理分析

目的 了解表现为少量蛋白尿和（或）血尿IgA肾病（IgAN）患者的肾脏病理特征及其与临床表现的关系。 方法 对1993年1月至2009年10月肾活检确诊为IgAN,且表现为少量蛋白尿 （<1 g/24 h）和（或）血尿,Scr<133 μmol/L的患者的临床和病理资料进行回顾性分析。病理学分级参照Lee分级及Katafuchi半定量积分标准。应用多因素logistic回归法分析肾脏病理损伤的危险因素。 结果 符合入选标准共316例,男123例,女193例,肾穿时年龄（33.10±10.69）岁。蛋白尿伴血尿占84.5%、单纯血尿占7.6%、单纯蛋白尿占7.9%。16.5%患者伴有高血压。CKD1、2、3期分别占76.9%、20.9%和2.2%。Lee Ⅲ级及以上患者占31.3%。52.8%患者有不同程度肾小球硬化;20.3%伴新月体形成;22.5%伴小管萎缩;16.8%有间质纤维化;24.7%有血管病变。肾小球硬化积分与估算肾小球滤过率（eGFR）呈负相关;与蛋白尿及平均动脉压（MAP）呈正相关。肾小管间质病变积分与eGFR及血红蛋白(Hb)呈负相关;与尿蛋白量呈正相关。血管病变积分与MAP呈正相关;与eGFR呈负相关(均P < 0.05)。多因素logistic回归分析结果显示,肾活检时尿蛋白量（OR = 8.564,P < 0.01）、Scr（OR = 1.031,P< 0.01）及Hb（OR = 0.975,P < 0.01）是肾脏病理损伤（LeeⅢ级以上）的独立危险因素。 结论 部分表现为少量蛋白尿和（或）血尿IgAN患者的病理改变并不轻,且肾功能已减退。尿蛋白量、Scr、Hb是预测肾脏病理损伤程度的独立危险因素。肾活检对这些患者明确诊断、判断病情和预后、制定个体化治疗方案十分重要。     

Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis

It has been proposed that renal tubular damage and chronic hydrocarbonexposure are causally related to progression of renal failurein primary glomerulonephritis. We examined the relationshipbetween hydrocarbon exposure and morphological parameters oftubulointerstitial damage in 59 patients with biopsy-provenprimary glomerulonephritis (proliferative, n = 52; membranous,n = 7). From a mean follow-up period of 6 years patients weredivided into two groups (GP) according to the presence or absenceof progressive renal failure (GP 1, n = 24 with progressiverenal failure) and (GP 2, n = 35 without progressive renal failure).The two groups were comparable in age, sex, duration of diagnosis(since the time of biopsy) and blood-pressure control. Patientswere blindly assessed for chronic hydrocarbon exposure by avalidated questionnaire. Biopsy cylinders were blindly assessedretrospectively for relative interstitial volume of the renalcortex by the point-counting method. In addition an assessmentwas made of the degree of fibrosis and chronic inflammatorycellular infiltrate. Hydrocarbon exposure score derived from the questionnaire untilthe time of renal biopsy correlated both with interstitial volume(r=0.55; P<0.001) and serum creatinine (r=0.46; P<0.001).Moreover, interstitial volume also correlated with serum creatinine(r=0.63; P<0.001). Chronic hydrocarbon exposure scores andrelative interstitial volume in the renal cortex at the timeof renal biopsy was significantly higher in GP 1 than GP 2 (P<0.001). The degree of interstitial fibrosis and chronic inflammatorycellular infiltrate was also significantly higher in GP 1 thanGP 2 (P<0.01). At the time of renal biopsy patients fromGP 1 had a significantly higher mean serum creatinine than inGP 2 but the degree of proteinuria and proportion of patientswith hypertension were similar. The result of this study suggests that chronic hydrocarbon exposureand tubulointerstitial damage are causally interrelated andmay be important risk factors in the progression of renal failurein patients with primary glomerulonephritis. ^*Presently Postdoctorate Research Fellow, University of ColoradoHealth Sciences Center, CO, USA.     

Positive and negative hepatitis B virus in renal biopsies of IgA nephropathy: an 85-case clinicopathological analysis

SUMMARY: The aetiological role of hepatitis B virus (HBV) antigens in IgA nephropathy remains uncertain. In a clinicopathological study, we examined 85 patients with primary IgA nephropathy divided into two groups depending on whether renal biopsy specimens were positive or negative for HBV antigens (HBsAg, HBcAg and HBeAg) using immunohistochemical methods. Compared with patients in the negative group ( n = 59), those in the positive group ( n = 26) had more obvious gross haematuria, proteinuria, hypertension and renal impairment. Their haemoglobin level, serum IgA concentration and creatinine clearance were also significantly abnormal. Immunofluorescence microscopy indicated that immunoglobulins deposited were mainly found in the combination of IgA + IgG + IgM. Consistent with the clinical manifestations, the pathological lesions revealed more glomerular sclerosis, tubular epithelial degeneration and necrosis and interstitial inflammation and fibrosis ( P < 0.05). Thus, we concluded that the presence or absence of HBV in renal tissue from patients with IgA nephropathy results in significant differences in the clinical features, types and severity of pathological lesions and, consequently, prognosis. Tissue deposition of HBV might play an aetiological role in the pathogenesis of IgA nephropathy and may be an exacerbating factor in renal progressive deterioration. Antiviral therapy could be an important intervention in HBV antigen-positive patients.